Genetic studies of the cycl gene in yeast along with protein analysis of its gene product iso-1-cytochrome c has led to the identification of UAA and UAG nonsense codons, missense mutants, frameshift mutations, and mutations of the AUG initiation codon. The nucleotide sequences of these mutational lesions were deduced from amino acid changes in altered, but functional, iso-1-cytochromes c. This iso- 1-cytochrome c system and the defined cycl mutants are being employed in numerous genetic studies, including investigations of mutagenesis, recombination and fine-structure mapping, nonsense mutants and their suppressors, initiation mutants and mechanisms of initiation of translation, and structure-function relationships. Many of the studies have included the following amino-terminal region iso-1-cytochrome c whose nucleotide sequence was deduced from amino acid changes in revertant proteins: (Met Thr-Glu-Phe-Lys-Ala-Gly-Ser-Ala-Lys-Lys-Gly- Ala- Thr-Leu-AUG ACU GAA UUC AAG GCC GGU UCU GCU AAG AAA GGU GCU ACA CUN.